The objective of this proposal is to study the mechanisms of normal and abnormal function of the basal ganglia and the relationship of these mechanisms to neurotransmitter function. This investigation will be made possible by the collaborative efforts of investigators in Pharmacology, Neurology, and Psychiatry at the University of Colorado Medical Center. Patients with Parkinsonism and other diseases of the basalganglia will be studied before and during treatment with L-dopa. Major and minor metabolites of L-dopa will be determined in blood, urine, and cerebrospinal fluid. Correlations will be made between the neurologic status and the metabolism of catecholamines with and without adjuvant therapy with a peripheral dopa decarboxylase inhibitor. The role of catecholamines in affective disorders will be investigated. The effects of L-dopa and other drugs which alter basal ganglia function upon mechanisms which regulate the synthesis of acetylcholine and catecholamines will be investigated. Because of a possible relationship between neurologic deficits and the degree of sulfate conjugation of metabolites of L-dopa, the relative capacities of the liver and brain to generate sulfate esters of L-dopa and its metabolites will be studied. Intact isolated Lewy bodies from the brains of patients with Parkinsonism will be analyzed to determine their exact biochemical characteristics. The role of glial cells in basal ganglia function and noradrenergic mechanisms will be investigated, as well as the effects of L-dopa on the function of glial cells.